1. With and without the 3 Mints
Angela Ho, Wade Morishita, Deniz Atasoy, Xinran Liu, Katsuhiko Tabuchi, Robert E. Hammer, Robert C. Malenka, and Thomas C. Südhof
You can tell a lot about a protein by what it hangs out with. The three Mints (also called X11-like proteins) bind to multiple synaptic proteins, and knock-out studies have suggested that they may indeed be necessary in synaptic transmission. But different isoforms can complement each other’s function; thus, it has been difficult to come to firm conclusions using single knock-outs. This week, Ho et al. deleted the Mints using constitutive and conditional knock-out strategies. Deletion of Mint 1 and 2, the two isoforms specifically expressed in neurons, caused most mice to die at birth. The 20% that survived had ataxia and reduced body weight. In the double knock-outs, whole-cell recording of hippocampal neurons revealed lowered synaptic strength, a twofold decrease in the frequency of miniature EPSCs, and enhanced paired-pulse facilitation, indicative of a presynaptic action of Mint 1 and 2. Similar results were obtained with acute ablation of Mint 1/2/3.
2. Born-Again Neurons in Mice and Men
John J. Ohab, Sheila Fleming, Armin Blesch, and S. Thomas Carmichael
and
Jadranka Macas, Christian Nern, Karl H. Plate, and Stefan Momma
Stroke doesn’t only cause cell death, but it also attempts at recovery through neuronal regeneration in tissues near the infarct, according to two separate studies published this week. Using histological analyses in a large collection of postmortem human brains, Macas et al. found increased numbers of neuronal precursor cells, even in patients of advanced age who had suffered ischemia. Because recent studies have coupled neurogenesis to the formation of new blood vessels, Ohab et al. tested the link in a model of focal stroke in mice. These authors showed that stroke induced the long-distance migration of thousands of newly born neuroblasts from the subventricular zone to peri-infarct cortex. The new cells associated with peri-infarct blood vessels in a region of active vascular remodeling. When Ohab et al. added stromal-derived factor 1 and angiopoietin 1, which are produced by the vasculature, the number of newly formed neurons increased.
3. Localizing Vocal Emotions
Jane E. Warren, Disa A. Sauter, Frank Eisner, Jade Wiland, M. Alexander Dresner, Richard J. S. Wise, Stuart Rosen, and Sophie K. Scott
The sound of laughter or cheering typically makes us smile or laugh. Warren et al. wanted to know how this happens. A facial expression showing an emotion can produce a so-called "mirror" response or similar facial expression in an observer. The authors used functional magnetic resonance imaging to determine whether similar mirror responses were also triggered by vocal expressions of emotion. Study participants were asked to listen to human voices conveying positive valence such as amusement and triumph. Listening to these "positive-valence" vocalizations activated specific premotor areas in the left posterior inferior frontal region, an area involved in control of facial movement. The activation was not attributable to facial movement per se. Thus, listening to vocal expressions of emotions appears to automatically engage preparation for orofacial gestures corresponding to the emotional content of the stimulus.
4. Ginkgo biloba and Oligomeric Aß in Worms
Yanjue Wu, Zhixin Wu, Peter Butko, Yves Christen, Mary P. Lambert, William L. Klein, Christopher D. Link, and Yuan Luo
Ginkgo biloba, the ancient plant that fed dinosaurs, is widely used in patients with Alzheimer’s disease AD). This week, Wu et al. examined the effects of a standard preparation of plant extract, EGb 761, in Caenorhabditis elegans. Nematodes do not express endogenous ß amyloid (Aß), the peptide that oligomerizes and form deposits in AD brains. Nonetheless, transgenic expression of Aß causes striking pathology in C. elegans, such as muscle paralysis and problems with chemotaxis, which were alleviated by EGb 761. Rescue of these behaviors was accompanied by a reduction in Aß oligomers. The beneficial effects of G. biloba are thought to result from neuroprotective and antioxidant properties. But in the transgenic C. elegans, reducing oxidative stress with the antioxidant L-ascorbic acid was not nearly as effective in suppressing paralysis as EGb 761. Thus, the beneficial effects of the extract may result from block of Aß oligomerization.